Effects of pivagabine on psychophysical performance and behavioural response in experimental models of stress

The effect of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg), a synthetic molecule with neuromodulatory activity, was evaluated on a series of behavioural parameters in rats exposed to various stimuli, with the aim of evaluating the response to stress (open field exploration, water maze, psychic conflict), conditioning (active and passive avoidance and avoidance retention, aggressiveness, extinction of conditioned responses), learning and performing of specific psychophysical tests (rota-rod, ballasted swimming, taut thread). Pivagabine induced significant improvement of stress-related tests by reducing the anxiety-producing reactions related to the various experimental settings. In conditioning tests an improvement in learning of conditioned responses was observed at lower dosages (10 and 50 mg/kg); an opposite effect was obtained with higher dosages (100 and 200 mg/kg). Pivagabine did not influence the retention nor the extinction of conditioned responses. Pivagabine induced a marked improvement of all motor performance tests in young and in aged animals. By contrast with benzodiazepines, pivagabine did not alter the ability of learning tasks, the motor performance and the aggressive behaviours. It is likely that the observed effects of pivagabine are mediated by inhibition of release of corticotropin-releasing factor, a neurohormone involved in stress-generating mechanisms.